Abstract The aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 and N = 47) were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with questionnaires and accelerometers. Several tests were conducted to estimate cardiorespiratory fitness and muscle strength. Body composition was estimated by dual-energy X-ray absorptiometry. DNAmAge estimates from blood and muscle were highly correlated with chronological age, but different age acceleration estimates were weakly associated with each other. The monozygotic twin within-pair similarity of ageing pace was higher in blood (r = 0.617–0.824) than in muscle (r = 0.523–0.585). Associations of age acceleration estimates with PA, physical function and body composition were weak in both tissues and mostly explained by smoking and sex. The muscle-specific epigenetic clock MEAT was developed to predict chronological age, which may explain why it did not associate with functional phenotypes. The Horvath’s clock and GrimAge were weakly associated with PA and related phenotypes, suggesting that higher PA would be linked to accelerated biological ageing in muscle. This may, however, be more reflective of the low capacity of epigenetic clock algorithms to measure functional muscle ageing than of actual age acceleration. Based on our results, the investigated epigenetic clocks have rather low value in estimating muscle ageing with respect to the physiological adaptations that typically occur due to ageing or PA. Thus, further development of methods is needed to gain insight into muscle tissue-specific ageing and the underlying biological pathways.

BACKGROUND: Bioimpedance skeletal muscle indices (SMI) are used as a surrogate for skeletal muscle mass, but their associations with physical functioning and obesity need further evaluation. AIMS: To compare the associations of body mass index (BMI), bioimpedance spectroscopy-based calf intracellular resistance (Cri-SMI), and single-frequency bioimpedance analysis (SF-SMI) indices with physical performance and the functioning of community-dwelling older people at risk of or already suffering from sarcopenia. METHODS: Pre-intervention measurements of the screened subjects and the participants of the Porvoo sarcopenia trial (N = 428) were taken. Cri-SMI, whole-body SF-SMI, and BMI were related to hand-grip strength, walking speed, short physical performance battery (SPPB), and the physical component of the RAND-36. RESULTS: Among the older people (aged 75-96), Cri-SMI correlated inversely with age (men r = - 0.113, p < 0.001; women r = - 0.287, p < 0.001), but positively with SPPB (r = 0.241, p < 0.001) and the physical component of the RAND-36 (r = 0.114, p = 0.024), whereas BMI was inversely associated with SPPB (r = - 0.133, p < 0.001) and RAND-36 (r = - 0.286, p < 0.001). After controlling for age, gender, and comorbidity, one unit of Cri-SMI (cm2/Ω) was associated with a 3.3-fold probability of good physical performance (SPPB ≥ 9 points, OR = 3.28, p < 0.001) and one unit of BMI (kg/m2) decreased the respective probability 4% (OR= 0.96, p = 0.065). Physical inactivity partly explained the negative association of BMI. When Cri-SMI and BMI were controlled for, a 1% difference in Cri-SMI was associated with a 0.7% (p < 0.001) higher probability of good performance, the respective figure being - 2.2% (p = 0.004) for BMI. The associations of SF-SMI with physical functioning indices were insignificant. CONCLUSIONS: Independent of each other, Cri-SMI was positively and BMI was inversely associated with the physical performance and functioning of community-dwelling older people who were at risk of or already suffering from sarcopenia. We found no association between SF-SMI and physical functioning.